In recent years, attention is drawn to the accumulation of sorbitol in cells via a polyol pathway, i.e. a metabolic pathway of glucose, as a causative factor of various complications of diabetes such as cataract, retinosis, keratopathy, nephrosis, peripheral nervous system disorder, etc. The polyol pathway, proved to occur widely in various internal organs by immunotissue-chemical means, is a metabolic pathway in which aldoses such as glucose, galactose, etc., are converted through polyols e.g. sorbitol, galactitol, etc., into ketoses such as fructose, etc.
The enzyme catalyzing the conversion of aldoses into polyols in the first step of this pathway is called aldose reductase, and is considered the rate-limiting enzyme in the polyol pathway. It was reported that various complications in patients with diabetes are effectively prevented and cured by inhibiting aldose reductase and lowering sorbitol production and accumulation (Pharmacia, 24: 459 (1988)).
Under the circumstances, the development of pharmaceuticals with an inhibitory action on aldose reductase has been desired.
As pharmaceuticals with an inhibitory action on aldose reductase, Japanese Patent Appln. LOP Publication No. 228,914/89 discloses chromone derivatives Capillarisin (R.dbd.H) and 7-methyl Capillarisin (R.dbd.CH.sub.3) isolated from the herb of Artemisia capillaris thumb, represented by formula: ##STR2##
Known compounds with a similar structure to Capillarisin include the chromone derivatives of formula (A): ##STR3## wherein R1, R2, R3, R4 and R5 are set out in Table 1 (for example, Japanese Patent Appln. LOP Publication Nos. 169,586/90, 114,768/79 and 322,066/88 and Journal of the Pharmaceutical Society of Japan, 96: 841 (1976) and 96: 855 (1976)). However, it has not be made evident whether these chromone derivatives have any inhibitory action on aldose reductase.
TABLE 1 ______________________________________ R.sub.1 R.sub.2 R.sub.3 R.sub.4 R.sub.5 ______________________________________ CH.sub.3 H O OCH.sub.3 CH.sub.3 CH.sub.3 CH.sub.3 O OCH.sub.3 CH.sub.3 C.sub.2 H.sub.5 H O OCH.sub.3 C.sub.2 H.sub.5 C.sub.2 H.sub.5 C.sub.2 H.sub.5 O OCH.sub.3 C.sub.2 H.sub.5 COCH.sub.3 COCH.sub.3 O OCH.sub.3 COCH.sub.3 H H S OCH.sub.3 H H CH.sub.3 O H H CH.sub.3 CH.sub.3 O H CH.sub.3 CH.sub.3 H O H H H H O H H H H O H CH.sub.3 CH.sub.3 H O H CH.sub.3 ______________________________________